An analysis of randomized trials indicates that compared with placebo, the magnitude of benefit of antidepressant medications varies with the severity of depressive symptoms, and may provide little benefit for patients with mild or moderate depression, but appear to provide substantial benefit for patients with very severe depression, according to an article in the January 6 issue of JAMA.

Antidepressant medications (ADM) are the current standard of treatment for major depressive disorder (MDD), but there is little evidence that they have a specific pharmacological effect relative to placebo for patients with less severe depression, according to background information in the article.

Jay C. Fournier, M.A., of the University of Pennsylvania, Philadelphia, and colleagues conducted a meta-analysis to estimate the benefit of ADM vs. placebo across a wide range of initial symptom severity in patients diagnosed with depression. The researchers combined data from 6 large-scale, placebo-controlled randomized trials. The studies included 718 adult outpatients.

The authors found that the efficacy of ADM treatment for depression varied considerably, depending on symptom severity. "True drug effects (an advantage of ADM over placebo) were nonexistent to negligible among depressed patients with mild, moderate, and even severe baseline symptoms, whereas they were large for patients with very severe symptoms."

"What makes our findings surprising is the high level of depression symptom severity that appears to be required for clinically meaningful drug/placebo differences to emerge, particularly given the evidence that the majority of patients receiving ADM in clinical practice present with scores below these levels."

"Prescribers, policy makers, and consumers may not be aware that the efficacy of medications largely has been established on the basis of studies that have included only those individuals with more severe forms of depression. This important feature of the evidence base is not reflected in the implicit messages present in the marketing of these medications to clinicians and the public. There is little mention of the fact that efficacy data often come from studies that exclude precisely those MDD patients who derive little specific pharmacological benefit from taking medications. Pending findings contrary to those reported here and those obtained [in previous studies] by Kirsch et al and Khan et al, efforts should be made to clarify to clinicians and prospective patients that whereas ADM can have a substantial effect with more severe depressions, there is little evidence to suggest that they produce specific pharmacological benefit for the majority of patients with less severe acute depressions," the authors conclude.